Harry Kane was left on the bench at the Westfalenstadion as Pochettino played Nacer Chadli up front and Ryan Mason and Tom Carroll in midfield and handed 18-year-old Josh Onomah only his fourth start of the season.
The decision to rest some of his top players, with Mousa Dembele also on the bench and Eric Dier left at home, backfired as Marco Reus' double and Pierre-Emerick Aubameyang's header all but ended Spurs' hopes of progress.
"No regrets," Pochettino said
"I'm very disappointed with the result but we didn't have a very good day. It was a bad day in the office.
"When we analysed the squad and picked the starting eleven we tried to win the game. It started okay but it was a really bad day for us."
The defeat leaves Tottenham with a mountain to climb in the second leg at White Hart Lane but also means Pochettino's men are now winless in three matches, following last week's loss at West Ham and draw with Arsenal.
A trip to bottom-of-the-table Aston Villa on Sunday offers the perfect chance to bounce back as Spurs look to resume a title challenge that has them sitting five points behind league leaders Leicester.
"I am not worried, I know the circumstances," Pochettino said.
"We need to accept some periods during 10 months that we will have good and bad times. We have always had things good.
"It has only been in the last few games not so much. The players are very sad but we have to take the positives.
"We have a big challenge against Aston Villa on Sunday. We are in a very good position in the league and we will do our best."
Source: PA