Borthwick's men are one of only two teams, along with champions Ireland, still in contention for a Grand Slam following narrow wins over Italy and Wales, but they have lost their past three matches against Scotland.
England finished third at last year's World Cup in France, while a Scotland side coached by Gregor Townsend failed to get out of the group stage.
Scotland edged Wales 27-26 in their Six Nations opener before falling agonisingly short against France in a 20-16 defeat.
Borthwick believes England will face an uphill struggle to regain the Calcutta Cup in front of a passionate crowd at Murrayfield.
"We're concentrating very much on Scotland, who are clearly favourites going into this fixture again with the record they've had," said the England boss. "They're very confident.
"This is a team where Gregor has been in place for seven years. It's a team that's been together a long time and is a very settled team.
"We're in a different situation to where they are."
Borthwick has made five changes to his starting XV from the team that edged Wales 16-14 but there are plenty of experienced campaigners involved.
Danny Care, in at scrum-half in place of the injured Alex Mitchell, will be winning his 99th cap on Saturday and fly-half George Ford his 94th.
Up front, props Ellis Genge and Dan Cole will pack down either side of captain and hooker Jamie George in a front row with more than 250 England Tests between them.
Borthwick, however, did spring a surprise by dropping full-back Freddie Steward, known for his solidity under the high ball, and recalling George Furbank to give England an extra attacking edge.
Furbank has won just six caps since his Test debut in 2000 but the 27-year-old has impressed for Premiership leaders Northampton.
"I think George has been exceptional all season for his club side," said Borthwick. "George is a guy who is high up on line-break assists across European and Premiership rugby, he is a very good player who I think is right for this game."
Furbank said he was now better prepared, both physically and mentally, for Test rugby.
"I've definitely grown as a player and a person," he said. "Literally...I've put on a bit of size which has helped my game. But I've also learnt a bit about the mental side of things as well which has definitely helped.
"And having a leadership role at Saints has definitely developed me as a character."
