It's "safe" aka not likely to wear anything out faster, since most vehicle hvac components run at a steady state no matter the input load, but you will likely see significantly reduced performance. Vehicle HVAC is always fighting a losing battle against a barely-insulated tin can that is about 50% thermally transparent glass. Any slight reduction in airflow is going to make it less comfortable and likely way worse at maintaining any in-cabin set temp.

I guess worst case, reduced airflow over the A/C evaporator could cause the compressor clutch to cycle on and off more frequently when running A/C.

Vehicles specced with HEPA filters from OEM usually have significantly larger filter area, to compensate for how restrictive the media is. If the OE filter isn't a HEPA I would not put one or any other super special "high efficiency" filter in.