The Eagles have faced adversity before during Head Coach Doug Pederson's tenure. It's not the first time a rash of injuries prevented several of the top playmakers from being on the field. How will this year's team respond? That question will begin to be answered on Sunday night in a prime-time showdown against the San Francisco 49ers, the defending NFC Champions who are also dealing with significant injury question marks.

The Eagles will be without the following: at least three of their top wide receivers (DeSean Jackson, Alshon Jeffery, and Jalen Reagor), four of their starting offensive linemen (Brandon Brooks, Andre Dillard, Jason Peters, and Isaac Seumalo), tight end Dallas Goedert, defensive end Vinny Curry, cornerback Avonte Maddox, and safety Will Parks.

Several key contributors, some who have not taken a snap for the team this season.

Meanwhile by the bay, the 49ers will be missing: quarterback Jimmy Garoppolo, running backs Tevin Coleman and Raheem Mostert, tight end Jordan Reed, defensive ends Nick Bosa and Dee Ford, defensive tackle Solomon Thomas, linebacker Dre Greenlaw, and three top cornerbacks (Richard Sherman, Emmanuel Moseley, and Ahkello Witherspoon).

These teams could field a talented squad of just injured players.

No one is feeling sorry for either of these teams.

The 49ers are 2-1 in a very tough NFC West. After losing in Week 1 to the Arizona Cardinals, the 49ers feasted on the two New York teams, beating the Jets and Giants by a combined score of 67-22.

The Eagles are 0-2-1 after last week's tie with the Cincinnati Bengals. Pederson was the offensive coordinator in Kansas City when the Chiefs started the 2015 season with a 1-5 record and won 10 straight games to earn a playoff spot. What are some of the things that Pederson can pull from that season – in addition to the past three years with the Eagles?

Let's get into the Game Preview, presented by Unibet.

Storylines to Watch

1. How do the Eagles get Carson Wentz on track?

Pederson said that the Eagles need to "unclutter" the quarterback's mind after a third straight game with multiple interceptions to open the 2020 season. The Eagles, after losing Goedert and Jackson in the first half against Cincinnati, did find a spark with Wentz's legs, as he churned out a career-high 65 yards on the ground, including the game-tying 7-yard touchdown run that sent the game to overtime. And looking back at the 49ers' Week 1 loss to Arizona, quarterback Kyler Murray led the Cardinals with 91 rushing yards and a touchdown. Pederson also hinted at an increase in utilizing tempo to dictate the pace of the game.

2. Will the Eagles have to rely on the 2019 offense?

It sure looks to be the case, but remember in the final four games of the regular season – all Eagles wins – Wentz threw seven touchdown passes and no interceptions. It will be different as the Eagles will be without Goedert, who was put on Injured Reserve, but the premise will be the same. The Eagles need to establish Miles Sanders and the rushing attack.

3. Who starts at left tackle?

In the fourth game of the season, the Eagles will start their fourth different offensive line combination. Jason Peters was placed on the Injured Reserve list Saturday with a foot injury. All signs point to Jordan Mailata, the seventh-round pick from Australia in 2018, getting his first career start. Time to find out if he can rise to the occasion against a defensive front that is still very good despite the injuries. Arik Armstead lines up at different spots along the line of scrimmage. Kerry Hyder and Ziggy Ansah and Dion Jordan are veterans who have helped keep the 49ers defense as one of the strongest units in the league. According to Football Outsiders, the 49ers have the fifth-ranked defense and are the third-best team overall.

4. What did the defense learn from the Rams game?

The Eagles will have a chance if the defense that showed up against Washington (2.2 yards per rush) or Cincinnati (eight sacks) shows up. If the one that had no answers for the Rams, it will be a long night and cross-country flight back to Philadelphia.

49ers Head Coach Kyle Shanahan employs a lot of the same pre-snap motion and misdirection plays to confuse defenses and free up his playmakers. The 49ers are also getting wide receiver Deebo Samuel back in the lineup and Samuel is someone who can make plays in both the passing game and the run game as well. All-Pro tight end George Kittle is also playing after missing two games with a knee injury to ease the pressure off starting quarterback Nick Mullens.

Defensive Coordinator Jim Schwartz blamed himself for a simple game plan against the Rams in Week 2. The 49ers are a disciplined team that doesn't make a lot of mistakes, but Schwartz will have a chance to redeem himself here.

Scouting Report

Eagles Game Plan analyst Greg Cosell on what the Eagles' offense could look like: "Tempo, no-huddle. I wouldn't be surprised if you start seeing some of that. I think most quarterbacks are comfortable with that. Most quarterbacks like to play fast. I think Carson likes to play that way.

"You got to orchestrate plays. You can't just rely on talent for plays to happen. You have to orchestrate and manufacture plays."

Greg Cosell on the 49ers' offensive formations: "The 49ers have been in a base personnel grouping (21, 12, or 22 personnel) on 65 percent of their offensive snaps."

Greg Cosell on 49ers fullback Kyle Juszczyk: "He's not an old-school fullback when you think of 20 or 30 years ago. He's a terrific blocker, but he lines up all over the formation. ... He's actually a very good receiver, not a volume receiver, but a very good receiver."

Greg Cosell on 49ers Head Coach Kyle Shanahan: "What Kyle Shanahan is really good at in my view, is understanding the responsibility of specific defenders and attacking those responsibilities, particularly defenders who have both a run and a pass responsibility. He's really good at identifying those players and putting them in conflict."

Greg Cosell on the Eagles' defense: "The Eagles are playing more man coverage this year. They're over 60 percent (of the snaps) man coverage through three games. They clearly have kind of moved in that direction."

Eagles Game Plan analyst Fran Duffy on wide receiver Greg Ward: "I would say he's the second-best route runner on the team right now behind Zach Ertz with what he's able to do to create that separation."

Greg Cosell on 49ers linebacker Fred Warner: "He can do so many things and the 49ers ask him to do a lot of things. Fred Warner is one of the most elite, special linebackers in the NFL. He's a player that the Eagles will have to be aware of in many different circumstances and down-and-distance situations."

By the numbers

8/1 – The Eagles have turned the ball over eight times and have a -7 turnover differential, the worst in the NFL. The 49ers have turned the ball over just once and have a +3 turnover differential – tied for fifth in the NFL.

100 – Miles Sanders has garnered at least 100 yards from scrimmage in four of his last five regular-season games.

187.3 – The 49ers allow the second-fewest passing yards entering Week 4, just 187.3 per contest.

30 – The 49ers are looking to score 30 or more points in three straight regular-season games in the same year since 2013.

4 – This is crazy. The 49ers have allowed opponents to reach the red zone just four times in the first three contests, first in the league.

Behind enemy lines

Tim Ryan, the 49ers' radio analyst, offers a peek behind the curtain at how the 49ers have stayed resilient despite a crushing Super Bowl loss and the injuries to start 2020.

How would you evaluate the mental resilience of a team that loses the Super Bowl, is dealing with significant injuries, yet finds a way to win?

"This is a mentally tough football team and I think it starts at the top. I think it start with the head coach in terms of the message that he's providing every day to those players and then the guys who pick the personnel, who I like to call paid professional observers of talent. They have gotten guys on this team that are mentally tough. When you endure those injuries, when you endure a Super Bowl loss and you're seven minutes away from a party with the Lombardi, that sticks with you. Then, you add the pandemic in and this is the year of the mentally tough. This is the year of the football team, the organization that can really keep their eyes on the prize despite all of these crazy dynamics."

What is an overview of the offense without Jimmy Garoppolo at quarterback?

"The run game wasn't great. I'll give you that. This team is always built on the run game and play-action and getting that stretch play to work. They (the Giants) run that 3-4 defense so it was hard to get the ball out on the edge. Really, the game was about ball control, team football, and Nick Mullens making the right decisions and getting the ball out on time.

"One thing about Nick and he didn't play last year, played a couple of years ago and you know the numbers from the first eight starts – threw for the fourth-most yards of any player in pro football since 1970, the modern era of football and there's been a lot of good ones delivering the mail. He's certainly talented in terms of being able to go to the right spot. I think his arm has gotten stronger, you could see some illustrations of that on the field against the Giants and throwing outside the numbers and hanging in the pocket for three and a half, four seconds and driving the ball into the middle of the defense off of his back foot. There were a few examples of that. But he's gonna be prepared. He knows the offense as well as anybody and I would say as well as any quarterback could know this offense."

How does a struggling Eagles offense that's got a ton of injuries attack San Francisco's defense?

"I think everybody needs to try to run the ball and San Francisco, this 49ers front, has been pretty damn good at defending running backs. Carson Wentz may have to get his lifestyle back up and we know his injury history, but Kyler Murray got 'em good on some scrambles. Kyler is going to do that to everybody for Arizona. (Jets quarterback Sam) Darnold got them for a scramble or two. (Giants quarterback) Daniel Jones him them with a couple of read-zones and really kind of caught them with their eyes in the backfield, and those were the biggest plays by the Giants.

"I think you've got to run the ball whether it's with your running backs or with your quarterback making timely runs with his legs, and then you've got to keep the quarterback clean in terms of the four-man rush. If the four-man rush is working, it's a challenge because this defense doesn't give up a lot of big plays. They're not gonna let you beat them over the top. Your quarterback's got to be patient. Your receivers, your tight ends, running backs, they got to break tackles when you feed them under those zones and some of that shell coverage. The 49ers want to rally up, they want to hit you, and they want to be fierce tacklers.

"I think it's a mix of everything but it really starts by being able to do your best to control that front and control that line of scrimmage."

Speaking of injuries

Eagles

Doubtful

• WR J.J. Arcega-Whiteside (calf)

Out

• WR DeSean Jackson (hamstring)

• WR Alshon Jeffery (foot)

• CB Avonte Maddox (ankle)

• T Jason Peters (foot/placed on IR)

• CB Trevor Williams (rib)

49ers

Questionable

• CB K'Waun Williams (hip)

Out

• DE Dee Ford (back)

• QB Jimmy Garoppolo (ankle)

• LB Dre Greenlaw (quadricep)

• CB Emmanuel Moseley (concussion)

• RB Raheem Mostert (knee)

• TE Jordan Reed (knee)

• CB Ahkello Witherspoon (hamstring)