Clicks/pops on start/stop not solved with buffer size

Hi all,
I run N7.1 on a 2011 IMac 2,5 GHz Intel Core i5) with 8 GB DDR3 a 1333 MHz + Rme Fireface 800 FW.
I’ve been using N4.3 on this system for the last years with no relevant issue and I recently upgraded to El Capitan 10.11.6 and to N7.1.
Everything went fine so far except for a couple of “video service not responsive” alerts (no crash) but I have this very annoying problem: audio clicking/popping everytime Nuendo starts/stops reproducing audio. You can hear clicks also when muting/unmuting audioclips and also when manually changing the volume clip: of course no click when hitting play/stop on the transport panel if no audio is actually present on the timeline and the starting point. I didnt notice any particular spike on the performance monitor except maybe for some spikes on the “disk” indicator, but I’m not sure it is related.
Of course I tried to change buffer size to the max but the problem is still there. Is there any other option inside Nuendo I should tweak regarding this? Or it is more probably OSX related?
Any help really appreciated!

I noticed that the disk indicator in VST performance is constantly flashing (and hitting the red zone) whenever i move the transport through the timeline, independently from the presence of audio clips. I tried opening a project saved on an external (usb) HD and the disk indicator is flashing in the same way. My internal HD is a 500 gb 7200 rpm and has more than 200gb of free space. I also tried switching the asio driver to “internal” and monitoring audio through the built in mac audio out but the audio clicks and pops are still there whenever an audio event is muted/unmuted, stopped/unstopped, its volume changed through handles.
This seems to me more system-related than a nuendo issue, any help to troubleshoot this is really appreciated.

Just noticed that the “clicking” sound I hear when muting/unmuting a clip with the “mute tool”, is affected by the eq/insert fx of the corresponding track: if I cut off the high freq the “clicking” sound is also cut off and if I put an fx, like a delay for example, the clicking sound is also delayed… Very weird.