Of course it will be much more difficult because you will be facing a team that is much more balanced and has almost the same level of experience. Porto is a representative who regularly enters the Champions League and of course their strength cannot be considered weak, especially if they play at home, so Arsenal needs to be aware of their ability to provide surprises. If I wanted to bet, I would prefer the match to end in a draw because after all, Porto is a team that is quite ready to play in the Champions League.
The match is still quite long and maybe both of them can prepare a lot, depending on the depth of the squad they have. When key players suffer injuries due to participating in the main league, this will actually affect the team's performance. Both coaches will have to get really good at rotating because the playoffs will be much more difficult.
One of the fixtures for the UCL round of 16 between Arsenal and Porto is more of an average probable game. Both teams are likely to win. Although Arsenal are a better side judging from their EPL performances, to their group stage performances too. Porto themselves aren't doing so bad in their league and they've got good track record in the group stage. That's why the game is going to be a little bit tough to predict the winner, well let's see if Arsenal would be able to comfortably win them and qualify for the next round.
Arteta's Arsenal are young, vibrant and victory oriented too. They won't want to give off their chances at the trophy just so easily to Porto. They're a side more likely to put up a fierce contest and make the game tough for their opponent Porto. Maybe or maybe not, Porto will be able to endure the strength Arsenal would put up. Arsenal are to some extent technically better than them still.