Question: Is it possible to reliably run a Pi in an airtight (watertight) case or is some form of ventilation required for cooling? I'm assuming it doesn't chuck out too much heat, but am wondering whether running it indefinitely this way may cause issues.

Answer: 
Based on my test Raspberry Pi runs relatively cool even when the CPU is 100% loaded for longer periods, so I think there shouldn't be a problem (I did not try loading the GPU though).
According to [this test](https://www.jeffgeerling.com/blog/2019/raspberry-pi-microsd-card-performance-comparison-2019) the USB 3.0 controller on Raspberry Pi 4 cannot work at full speed if there is no fan. The slow down without a fan could be 2-3 times. In the test the maximum speed was 346 MB/s for USB 3.0 (for comparison, it was 44 MB/s for an SD card). So depending on your speed requirements and how often you need it, you may or may not need active cooling.