After a bit of mucking about it lives!

It turns out the optocouplers are wired up in an inverting mode, so the UART doesn't work at all. Here's the original optocoupler (reverse engineered) schematic:

The SAMC21 (nor any of the SAMx2x microcontrollers) doesn't allow you to invert the hardware UART polarity, so you would have a tricky time getting a software UART working if you want to use the Arduino bootloaders (you could forego the bootloader, but where's the fun in that?). Now theoretically, you could use a UART->USB controller that had inverted logic, but most don't seem to.

So instead, there was enough free pads around the UART connectors (these were originally put in to be able to change the RX/TX orientation if necessary) to wire in some SOT-23 PNP based inverters while keeping things relatively neat (take note that the transmit LED needs a current limit resistor too otherwise you just get spikes on the UART bits as the LED starts to dim/burn out due to excess current):

As for the bootloader/core, I'm using a modified mattairtech ArduinoCore-samd (which is a modified ArduinoCore-samd) firmware which has options for the SAMC. The pinouts have changed of course, so a recompile of the bootloader is necessary to get things running.