Automotive MCUs
The auto world already uses plenty of different instruction sets: Power, ARM, Aurix, STM 16 bit, japanese Hitachi-PDP11 (no joking), japanese Mitsubish and probably 25 other instruction sets. It looks like the japanese now switch to ARM and use these controllers also in cameras, TVs etc.
That is possible, because automotive control units are custom-developed from pcb to housing to connectors to software. There is now some standardization from the AUTOSAR operating system, which is typically delivered in source by Vector Informatik. Modern auto software is fully done in C and is (to 99,99% of code) only a recompile away from a new mikrocontroller, if Vector Informatik has ported the OS to this MCU. Drivers are a different story, of course as they must fit to the MCU registers.
The control unit developer company must then demonstrate that the unit will meet all requirements defined by the auto company for the unit (including timing requirements). Unit and software testing should be done on the new controller to see that the compiler and the processor dont have funny behaviour. There is no additional effort for a new instruction set to perform this. Rather, the big effort is to define, create and debug all of these test cases.
In the IT sphere, a properly developed C++, Rust or Sappeur program will simply rebuild and run nicely on any major POSIX platfrom and CPU. If not, it is almost always due to a hidden bug. I have done this with great success from SPARC to ARM to ELBRUS:
http://sappeur.ddnss.de/
http://gauss.ddnss.de/
For example, the ELRBUS instruction set is a secret, but there exists a nice tcc C++ compiler. I never bothered to look at the generated binary code, it just runs quite nicely at approx RPI speed.