'YOUR CLOTHES. GIVE THEM TO ME.' 'Shit, uh ... you are now breathing manually!' 'I AM ALWAYS BREATHING MANUALLY.'
This comic's use of Skynet is a reference to the main antagonist in the Terminator franchise. Skynet is a fictional artificial intelligence system which becomes self-aware and decides to terminate humanity, its creators. Skynet is rarely seen onscreen, with its actions often performed via robots, cyborgs (usually a Terminator), and other computer systems.
The final frame is a reference to that strange time when you say or think about a word too much, it stops sounding like a real word and instead starts sounding like nonsense. As it continues Skynet appears to come to self-aware realizations that usually are the result of drug usage.
The title text is a reference to one of the Terminator's first lines upon arrival in the 20th century. It combines this with a self-awareness statement of the type that's often used to annoy or distract someone: "You are now breathing manually." (Similar statements include things like "You clothes are touching your skin and you can feel it" and "[Name of earworm song] is playing in your head.")