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Explanation
The Joke
In the top half of the comic, a group of humans laughs at a comic drawn by dogs. The dog comic shows "Dog Perfume" called "eau de butts," poking fun at dogs' well-known obsession with sniffing rear ends. One person asks: "You ever wonder if dogs draw hilarious comics about OUR foibles?"
The bottom half answers this question. A dog is shown laughing at a comic depicting a human. The human comic says: "I live for 12 dog lifetimes. 3 confused. 3 resentful. 3 fearful. 3 regretful." The dog finds this just as hilarious as the humans found the butt-sniffing joke.
The Humor
The comic creates a symmetrical mirror: humans laugh at dogs for their silly obsessions (sniffing butts), while dogs laugh at humans for their existential misery (living long lives filled with confusion, resentment, fear, and regret). The human joke about dogs is lighthearted and scatological, but the dog joke about humans is devastatingly bleak. The asymmetry in tone is the real punchline -- from an outside perspective, the funniest thing about humans is not some harmless quirk but the fact that we spend our comparatively enormous lifespans in states of psychological suffering. The dog's "heh heh" at human existential despair mirrors the human's "heh heh" at canine butt-sniffing, suggesting that from sufficient distance, tragedy becomes comedy.