S2 however (at least I think) should feature VA Janeway because of Chakotay, etc.
Also, with Mulgrew being part of the series from the start, do we have any indication that she won't be technically part of the series anymore?
Furthermore... if the Protostar is destroyed (and holo-Janeway too), how would she make a come back from the future when Chakotay sent the Protostar with holo Janeway into the past?
The possible solution to this would be the kids end up in the future and prevent the Protostar from being weaponized in the first place. Events unfold for the most part as they do, but the crew 'insulate' the Protostar from being hacked by the Construct (even if its still placed onto the ship), so opening hails to SF ships would not cause them to destroy themselves.
Even if the present-day Protostar gets supernova'd, Mulgrew would still be part of the series, with VA Janeway still around (we may get a scene of VA Janeway being debriefed by Jellico and/or various admirals/officials regarding what happened, for example) and a version of holo-Janeway likely present on a Protostar between the time that it arrived on Solum and was sent on its way again. In that case, they would likely attempt to stop the construct from even getting placed and/or armed.
If the Protostar is destroyed, the Dauntless (for which CGI 'sets' have been created) would probably temporarily takes its place as the "hero ship", with VA Janeway leading the mission to retrieve Chakotay (and the teens at some point getting away, somehow, on the Protostar again, possibly with tacit approval of Janeway and Chakotay).
I think John Noble may be back as well, voicing a younger version of himself and possibly also the older version either in narrated flashback or in the future with Chakotay.
As for nobody knowing what the Vau N'akat are: Starfleet will know as soon as they finish debriefing Janeway. The head of Starfleet Intelligence will be a Romulan agent, in a not too distant future, and is probably rising in the ranks already. Which means the Romulans will be aware too (and they will be interested after the events at Noble Isle, where they met several "interesting" individuals), through her or through other means of the Tal'Shiar. Starfleet and the Federation generally aren't great at keeping secrets, once those are not restricted to a very limited number of people (like Ross and Sisko).
The Klingons saw and heard Gwyn, and as they no doubt have a species database too, they will realise she is from an unknown species (and probably that those apparently are extremely good at learning languages). Same goes for the Ferengi.
And I agree with Timofnine that explanations will be demanded, now that at least the Klingons lost a vessel or vessels. Starfleet will have to tell them something, and if they lie they risk the Romulans knowing well before their allies, who came to aid them. Not a very Starfleet thing to do.
Section 31 will know, too. If Starfleet is not inclined to do anything about the threat, they will probably seek a way to do so in their stead. Who knows what they would do?
But - except for Ascensia - isn’t it true that none of them know where Solum is? Seems like you need a “search for Solum” theme?
The Diviner would know so too, and Gwyn did receive a final telepathic communication from him when he died. Vau N'akat seem to be capable of wireless information transfer, Cylon style (but short range, more bluetooth than interstellar), not only with their "heirlooms" but also with each other. So she may know.
Beyond that, the navigation computers of the Rev-12 and its sistership operated by Ascencia (which I'm guessing she may be heading too) would probably also have the location of Solum. Finding the Rev-12 would be difficult but not impossible, and Ascencia may seek out Starfleet installations herself, in an attempt to do more damage, once she realises her plan has not worked as well as she had hoped. This may in turn offer a chance to Starfleet to capture her and/or her vessel.
Starfleet is also likely to discover Solum on its own, on condition that the scheduled deep-space exploration (probably of the Delta quadrant, though we don't know that for sure yet) would be maintained.