Their use of addressing by keys instead of by IPs seems to be the main differentiator. Also the support for custom transports (BLE, LoRa, Tor) which appears to be in progress and not yet fully implemented.

I love Tailscale, it's deployed on all my devices. But I might check this out for the transports part in particular.

My 5 second summary: Tailscale connects devices and Iroh connects applications.

Tailscale is built to be global to your device, while iroh is built to be embedded into each application. This allows application developers and users a much more fine grained and bespoke setup, than having a single global bridge.