Sounds like you are heading west-to-east. Big difference.
Strong westerlies make westbound riding brutal in the Columbia Gorge via the L&C.
But eastbound it makes for easy riding - usually, not always.
If you are starting both at Astoria, the TransAm is longer, more remote, more consistently scenic.
The L&C has some spectacular scenery in the Columbia Gorge, but meh in the east.
The new Mitchell Point bike trail tunnel is due to be completed this April as part of the Old Columbia Highway Trail.
But you still have to ride stretches of a very busy I-84 between incomplete sections.
Wash Hwy 14 on the other side is narrow with no shoulders and fairly busy - so worse.
If you have the time, I'd do the original TransAm.
The coast section is somewhat busy on US 101, better on the back roads.
The Willamette Valley is fairly easy riding and gentle.
McKenzie Pass is way better than Santiam, but opens late some years. (Probably 2024)
Eastern Oregon is sweet cycling with small towns often enough for services.
White Bird Pass in Idaho is a bear - make sure to take the old road.
The first section of the L&C out of Astoria isn't great. The Washington side is much better.
No matter which side you are on, you have to get thru Portland metro area.
There are great bike trail; however, there are also large homeless encampments.
Some people are legit homeless, others are strung out on alcohol and drugs.
From Troutdale to The Dalles, the Old Columbia Highway Trail is spectacular.
There are sections of the old highway that are bike/ped only. Mind-blowing.
But you are always close to I-84 and the mainline railroad, so you don't reel remote.
East of The Dalles you cross over to Washington and a pretty barren landscape.
In Idaho, so NOT stay on US 12 even though it is a lower route - go thru Winchester.
PS - Time of year matters.
Warm and especially dry weather comes late to the Cascades.
An early start might be best on the L&C.
Late summer means fires and smoke.
Pics -
Historic Columbia River Highway Bike Trail Section
John Day Canyon on the Eastern Side of the Cascades