Napoli were level at half-time after McTominay cancelled out Jan Bednarek's early opener, but Gabri Veiga, Jakub Kiwior and Samu Aghehowa's late penalty condemned the Italian side to a heavy defeat at the Estádio do Dragão.
Højlund was particularly unhappy with the team's overall performance, rejecting the suggestion that Napoli had played well despite remaining competitive for much of the contest.
"We have to improve. We are really going through a dark period of our season. Everyone has to work to get better. I don't agree that we played a good game. We didn't play well. We have to stop losing matches because now there have been too many," the striker told Prime.
The Denmark international insisted that responsibility could not rest with one individual, calling on everyone at the club to examine their contribution.
"Everyone has to look at themselves in the mirror. We all have to take responsibility, from the players to the coach and the club."
McTominay was equally forthright following the defeat, making clear that Napoli's injury problems could not be used to excuse their performances.
"We have to play better in both boxes. We cannot continue like this. We lost 4-1, so of course I am angry. We have a lot of injuries, but that cannot be an excuse, even if the same players are always having to play."
The Scotland international acknowledged the frustration caused by the number of players unavailable, but stressed that injuries were part of football and the squad had to find solutions.
"Injuries are part of football, but we have far too many. I cannot explain how angry I am. Everyone has to go home and think about what they can do to improve tomorrow."
McTominay also highlighted the importance of Napoli addressing their shortcomings at both ends of the pitch, particularly after Porto punished them from set-pieces.
Højlund's demand for accountability and McTominay's anger reflected the mood inside the Napoli dressing room after a damaging European night.
With the defeat exposing defensive weaknesses and extending a difficult spell, the message from two of the team's leading players was unmistakable: Napoli must improve collectively, and nobody can avoid responsibility.