If anyone finds this thread like me and is having a similar problem, I could fix my problem.
After putting in a full backup of one of my servers, the datastore couldn't be validated.
"describedatastore.bat" showed the error "The data store machine may not have been initialized".
When opening the datastore config page in IE, the datastore expected me to first time configure it. (wich was wrong, because it had been configured)
After searching for a while, I found that in the data store config folder ("[installpath]\datastore\etc") the file "relational-config.json" was missing.
Only a "relational-config.json.backup" and "relational-config.json.history" where present.
I copied the "relational-config.json.backup" and renamed it to "relational-config.json".
After a restart of the portal and datastore service, everything was working again.
PS: I have no clue, why the config had been renamed...