Hello! I hope you've found a solution already, but if not, here are a few tips:

PRIMER can be quite demanding with large datasets, so try running it in priority mode with as much memory and CPU as possible. Close other programs, disable energy saving mode, and consider running it overnight.. (with Windows updates disabled).

Check your data for missing values or redundant rows, as these can slow down processing significantly.

If it’s an option, you could subsample or average your data to reduce size but keep in mind this may reduce variability, so consider if that fits your needs.

Finally, you might try the vegan package in R to run PERMANOVA. With one factor, it’s straightforward and you can adapt permutations and residuals options to be similar to PRIMER.

Best from Ulm, Katja