The eternal battle between Big-Endian (BE) and Little-Endian (LE) processors, illustrated perfectly by... people walking upside down?
For the uninitiated: endianness determines how bytes are ordered in memory. Big-endian puts the most significant byte first (like reading a number left-to-right), while little-endian puts the least significant byte first (reading right-to-left).
The comic shows a BE person trying to communicate with an LE person who's literally upside down, speaking in reverse syntax: "Processor? Central the to way the me tell you could lost. I'm" and "Much! Very you thank."
After 15 years in systems programming, I still have nightmares about debugging network protocols between different architectures. Nothing like spending three days tracking down a bug only to discover it's a byte-order issue. Endianness: the original "works on my machine" problem.