For a reflowable EPUB you can use an
SVG wrapper around images to make them fit as large as possible on the screen without distortion. That should work in calibre and many EPUB readers.
Another approach is to create a fixed-layout EPUB. Support for that within calibre is very limited. For other platforms support varies and may require proprietary markup.
On the Kindle platform comic viewing works in KF8 (azw3) and KFX formats, but not MOBI without KF8. The proprietary markup needed is documented in the
Kindle Publishing Guidelines. It will likely be easier to produce a Kindle comic using software such as
Kindle Comic Converter or Amazon's
Kindle Comic Creator. If your comic has panels the Kindle can allow viewing it either page-by-page or panel-by-panel.
Another alternative is to use a comic-specific format, such as CBR or CBZ. You can read that in calibre and in comic-specific apps, but not on Kindle.
(This thread will likely be moved by a moderator since it is not appropriate for the calibre development sub-forum.)